S. Carolina Pharmaceutical Research, Spartanburg, SC, USA.
Pulm Pharmacol Ther. 2012 Dec;25(6):465-71. doi: 10.1016/j.pupt.2012.08.007. Epub 2012 Aug 31.
Umeclidinium (UMEC; GSK573719) is a new long-acting muscarinic antagonist (LAMA) currently in development in combination with vilanterol (VI), an inhaled, long-acting beta₂ agonist for the treatment of chronic obstructive pulmonary disease (COPD). The primary aim of this study was to evaluate the safety and tolerability of repeat dosing of UMEC and VI in combination once daily for 28 days in patients with COPD.
This was a multicenter, double-blind, placebo-controlled, parallel group study. Patients aged ≥40 years with post-bronchodilator FEV₁ ≤80% of predicted normal values and FEV₁/FVC ratio ≤0.70, and a smoking history of ≥10 pack-years, were randomized 4:1 to once-daily UMEC/VI (500/25 mcg; n = 42) or placebo (n = 9).
UMEC/VI was non-inferior to placebo in weighted mean pulse rate over 0-6 h at Day 28 (primary endpoint: difference of -0.5 bpm, 95% CI: -5.5 to 4.5). There was no evidence of a difference between UMEC/VI compared with placebo in blood pressure, minimum and maximum pulse rate, or QTcF assessments. Adverse events (AEs) were reported by 11 (26%) patients in the UMEC/VI group and one (11%) patient in the placebo group. No serious AEs were reported. Both UMEC and VI showed rapid absorption (median t(max) ∼6 min for both drugs) with no evidence of accumulation for AUC or C(max) on Day 28 compared with Day 1 for UMEC or VI. There was no correlation between individual steady-state C(max) and pulse rate on Day 28. Change from baseline in trough FEV₁ on Day 29 showed numerically greater improvements with UMEC/VI compared with placebo.
Once-daily dosing with UMEC in combination with VI in patients with moderate-to-very-severe COPD was well tolerated over 28 days.
乌美溴铵（UMEC；GSK573719）是一种新型长效毒蕈碱拮抗剂（LAMA），目前正在与维兰特罗（VI）联合开发，用于治疗慢性阻塞性肺疾病（COPD）。本研究的主要目的是评估 COPD 患者每日一次重复使用乌美溴铵和维兰特罗联合治疗 28 天的安全性和耐受性。
这是一项多中心、双盲、安慰剂对照、平行组研究。年龄≥40 岁，支气管扩张剂后 FEV₁≤预计正常值的 80%，FEV₁/FVC 比值≤0.70，且吸烟史≥10 包年的患者，按 4：1 随机分为每日一次乌美溴铵/维兰特罗（500/25 mcg；n = 42）或安慰剂（n = 9）组。
乌美溴铵/维兰特罗在第 28 天 0-6 h 的加权平均脉搏率与安慰剂相比无差异（主要终点：差异为-0.5 bpm，95%CI：-5.5 至 4.5）。与安慰剂相比，乌美溴铵/维兰特罗对血压、最小和最大脉搏率或 QTcF 评估没有差异。乌美溴铵/维兰特罗组有 11（26%）例患者和安慰剂组有 1（11%）例患者报告发生不良事件（AE）。无严重 AE 报告。乌美溴铵和维兰特罗均显示快速吸收（两药的中位 t(max)约为 6 分钟），与乌美溴铵或维兰特罗的第 1 天相比，第 28 天的 AUC 或 C(max) 无蓄积。第 28 天的个体稳态 C(max)与脉搏率无相关性。第 29 天的谷值 FEV₁较基线的变化显示，乌美溴铵/维兰特罗组的改善程度大于安慰剂组。
在中重度至极重度 COPD 患者中，乌美溴铵与维兰特罗联合每日 1 次给药，28 天耐受性良好。
